Specific problems which relate to hormone action and intermediary metabolism will be studied: 1. Control of insulin secretion: Utilizing in vivo models such as the intact rabbit and in vitro models such as pancreatic pieces or isolated islets we will continue to investigate the mechanisms involved in the control of insulin secretion. Particular emphasis will be placed on the role of intracellular and extracellular monoamines (catecholamines and indoleamines) as inhibitors of the secretory process. 2. Hormonal regulation of cartilage metabolism: The effects of hormones (somatomedins, insulin, prostaglandins, etc.) and substrates on the control of cartilage growth and maturation will be studied using cartilage from 10 to 12 day old chick embryos as the test system. Specific emphasis will be directed toward elucidating the mechanisms by which somatomedins and insulin exert their effects on the synthesis of cartilage macromolecules. The role of free fatty acids as inhibitors of somatomedin stimulation of cartilage macromolecular synthesis and prostaglandin A1 as an inhibitor of both basal and stimulated states will be further defined. The regulation and function of cartilage cyclic AMP will be studied.